Anterior cruciate ligament (ACL) injury can lead to lifetime functional disability and early-onset knee osteoarthrosis (OA). Though ACL reconstruction surgery may restore function (at least in the short term), the procedure is not protective against OA. This is most likely due to a combination of two factors. First, reconstruction does not restore normal dynamic knee function, potentially exposing the joint to damaging loads. Second, the ACL-injured joint is subject to damage to other joint structures (particularly the meniscus) that may increase the sensitivity of the joint to damage from altered mechanics, predisposing it to long-term degeneration. The relative importance of these factors, as well as the relationships between ACL injury/reconstruction, dynamic knee function and long-term joint health, are unknown. We have developed novel methods (250 frame/s stereo x-ray) uniquely capable of characterizing in vivo tibio-femoral joint motion, including interaction of the articulating surfaces, during stressful tasks with very high accuracy (q0.1 mm). In the previous project period, we identified significant differences in dynamic joint function between human ACL-reconstructed and contralateral (uninjured) knees, as well as changes in graft and joint mechanics over time. Our goals now are to understand why these abnormal motions occur, and how they may be related to long-term degenerative changes in menisci and cartilage. Our preliminary data suggests that dynamic knee function may be related to ACL graft tunnel positions and meniscal condition, and Aim I investigates how these factors contribute to abnormal dynamic knee function. In Aim II we will determine if abnormal kinematics stabilize or continue to progress over time. Aim III addresses the relationship between abnormal joint kinematics and long-term changes in meniscus and cartilage condition. To address these Aims, 3D knee kinematics will be determined during stressful tasks using our unique dynamic stereo x-ray techniques. Meniscal damage will be assessed with serial MRI, and changes in cartilage thickness over time will be measured using Dynamic Joint Space analysis (a newly developed, sensitive in vivo method for measuring 3D functional joint space). This prospective, longitudinal study will combine a cohort of subjects from the previous period with newly recruited subjects (from the first 2 years of the new period). This will provide sufficient follow-up (3-10 years) to identify meniscal/cartilage damage in a significant subset of subjects, and relate it to dynamic knee function. This project will identify specific mechanical factors that contribute to joint degeneration after ACL reconstruction. This will provide a basis for the design and evaluation of treatments for improving the long- term outcome after ACL injury, as well as provide new insights into mechanical factors associated with degenerative joint disease in the knee.